Assessment of the circulating klotho protein in lung cancer patients

Abstract

The anti-aging factor, klotho has been identified as a tumor suppressor in various human cancers, including lung cancer. In vitro studies provided evidence that klotho expression influences the characteristics of lung cancer cells, however, in vivo results are lacking. The aim of our study was to evaluate whether circulating klotho protein might serve as a potential biomarker of lung cancer. Blood samples were taken from 45 newly diagnosed lung cancer patients (31 NSCLC, 14 SCLC) and 43 control subjects. Plasma klotho concentration was measured using ELISA. No difference in plasma klotho values was detected between patients and control subjects (366.3 (257.9-486.8) vs. 383.5 (304.6-489.7) pg/ml respectively (median (IQR)); p > 0.05). Plasma klotho levels in patients with distant metastasis did not differ from less advanced stage disease (354.2 (306.9-433.3 vs. 328.5 (242.5-419.7) pg/ml, p > 0.05). In contrast, analyzed with one-way ANOVA, significant difference (p = 0.04) was found between the examined histological types of lung cancer: adenocarcinoma (353 (329.4-438.5) pg/ml), squamous cell carcinoma (308 (209.6-348.1) pg/ml) and small cell lung cancer (388.8 (289.9-495.4) pg/ml). However, Tukey's post hoc test did not reveal significant difference between any pairs of histological groups. There was no difference between any histological subtype and health either. Our results suggest that circulating klotho protein cannot be considered as a biomarker for lung cancer. Further studies are warranted in order to examine the relationship between klotho expression in lung tissue and circulating levels of the protein, and to explore its mechanism of action in lung cancer.

Decreased Levels of Anti-Aging Klotho in Obstructive Sleep Apnea

“…Moreover, similar to our previous report, 24 we found unexpectedly high plasma klotho levels in some control participants. These subjects did not differ in terms of demographics or comorbid profile from other controls, and the reason for high klotho levels needs to be explored as these may potentially explain protective mechanisms against aging, inflammatory, and oxidative stress-related events.…”

“…Plasma klotho levels were measured using a commercially available ELISA kit (Immuno-Biological Laboratories Ltd.) as described previously. 24,25…”

Undetected αKlotho in serum is associated with the most aggressive phenotype of breast cancer

“…The data obtained in the present study proved that the concentration of αKlotho was not different between breast cancer patients and controls. These results are in agreement with those of a study on patients with lung cancer, which exhibited no differences in Klotho concentrations when compared to controls ( 63 ). In the present study, the control group was composed of patients' relatives, which may be a potential limitation for the detection of Klotho, as the family history of breast cancer may have had an influence.…”

SHANK1 facilitates non-small cell lung cancer processes through modulating the ubiquitination of Klotho by interacting with MDM2

“…Recent studies suggest that SHANK1 proteins are essential to developmentally regulating the activation of Akt and correlated intracellular pathways crucial for mammalian postnatal brain development and synaptic plasticity, while the detailed molecular function of SHANK1 is largely unknown. We reported previously that KL serves as a tumor suppressor gene in NSCLC, and that it inhibits the process of NSCLC [ 15 , 20 , 23 – 26 ]. We wanted to investigate whether SHANK1 plays a role in the expression or function of KL.…”